title: Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues.
abstract: BACKGROUND
  Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for differential post-operative diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples.
  
  
  METHODS
  A molecular classifier was created based on a combined analysis of two microarray datasets (using 66 thyroid samples). The performance of the classifier was assessed using an independent dataset comprising 71 formalin-fixed paraffin-embedded (FFPE) samples (31 FTC and 40 FTA), which were analysed by quantitative real-time PCR (qPCR). In addition, three other microarray datasets (62 samples) were used to confirm the utility of the classifier.
  
  
  RESULTS
  Five of 8 genes selected from training datasets (ELMO1, EMCN, ITIH5, KCNAB1, SLCO2A1) were amplified by qPCR in FFPE material from an independent sample set. Three other genes did not amplify in FFPE material, probably due to low abundance. All 5 analysed genes were downregulated in FTC compared to FTA. The sensitivity and specificity of the 5-gene classifier tested on the FFPE dataset were 71% and 72%, respectively.
  
  
  CONCLUSIONS
  The proposed approach could support histopathological examination: 5-gene classifier may aid in molecular discrimination between FTC and FTA in FFPE material.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, Gliwice 44-101, Poland. bjarzab@io.gliwice.pl.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Bartosz
authors.initials: B
authors.lastname: Wojtas
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Oczko-Wojciechowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kukulska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Czarniecka
authors.forename: Markus
authors.initials: M
authors.lastname: Eszlinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Musholt
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stokowy
authors.forename: Michal
authors.initials: M
authors.lastname: Swierniak
authors.forename: Ewa
authors.initials: E
authors.lastname: Stobiecka
authors.forename: Dagmara
authors.initials: D
authors.lastname: Rusinek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Tyszkiewicz
authors.forename: Monika
authors.initials: M
authors.lastname: Kowal
authors.forename: Michal
authors.initials: M
authors.lastname: Jarzab
authors.forename: Steffen
authors.initials: S
authors.lastname: Hauptmann
authors.forename: Dariusz
authors.initials: D
authors.lastname: Lange
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D003937:Diagnosis, Differential; D005557:Formaldehyde; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011184:Postoperative Period; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde